RNF168 E3 ligase participates in ubiquitin signaling and recruitment of SLX4 during DNA crosslink repair

Yoko Katsuki, Masako Abe, Seon Young Park, Wenwen Wu, Hiromasa Yabe, Miharu Yabe, Haico van Attikum, Shinichiro Nakada, Tomohiko Ohta, Michael M. Seidman, Yonghwan Kim, Minoru Takata

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

SLX4/FANCP is a key Fanconi anemia (FA) protein and a DNA repair scaffold for incision around a DNA interstrand crosslink (ICL) by its partner XPF nuclease. The tandem UBZ4 ubiquitin-binding domains of SLX4 are critical for the recruitment of SLX4 to damage sites, likely by binding to K63-linked polyubiquitin chains. However, the identity of the ubiquitin E3 ligase that mediates SLX4 recruitment remains unknown. Using small interfering RNA (siRNA) screening with a GFP-tagged N-terminal half of SLX4 (termed SLX4-N), we identify the RNF168 E3 ligase as a critical factor for mitomycin C (MMC)-induced SLX4 foci formation. RNF168 and GFP-SLX4-N colocalize in MMC-induced ubiquitin foci. Accumulation of SLX4-N at psoralen-laser ICL tracks or of endogenous SLX4 at Digoxigenin-psoralen/UVA ICL is dependent on RNF168. Finally, we find that RNF168 is epistatic with SLX4 in promoting MMC tolerance. We conclude that RNF168 is a critical component of the signal transduction that recruits SLX4 to ICL damage.

Original languageEnglish
Article number109879
JournalCell Reports
Volume37
Issue number4
DOIs
Publication statusPublished - Oct 26 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology

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